Area Under the Concentration Versus Time Curve for 0 to 24 Hours After Drug Administration, Done Between Days 9 and 12 of the Menstrual Cycle at Time 1 (Before) and Time 2 (During Treatment With St. John's Wort or Placebo) [ Time Frame: Area Under the Concentration versus Time curve for 0 to 24 hours after drug administration, between Days 9 and 12 of the menstrual cycle, done at Time 1 and at Time 2 ] [ Designated as safety issue: No ]

Pharmacokinetic studies were done between Days 9-12 of the menstrual cycle at Time 1 (baseline, before any treatment with herb or placebo), and at Time 2 (intervention, after treatment with herb or placebo).

12 serum samples drawn from 0 to 24 hours of administration of a dose of levonorgestrel.

Treatment between the two time periods was with St. John's Wort or placebo herb, beginning after the Time 1 (baseline) and continued for 5 weeks until Time 2.

Estimates of levonorgestrel clearance were made using a two stage non-compartmental approach to determine individual and group parameters.

Number of Participants With Progesterone Levels Above 3.0 ng/ml at Time 1 (Baseline) and Time 2 (After Intervention With St John's Wort or Placebo). [ Time Frame: Progesterone levels drawn at weekly intervals after dosing with levonorgestrel between Days 9 and 12 of the menstrual cycle, at each time point until menses ] [ Designated as safety issue: No ]

Serum progesterone levels were drawn at the time of dosing with levonorgestrel and then at weekly intervals until menses occurred. This was done at Time 1 (baseline), and again at Time 2 (after 5 weeks of dosing with St. John's Wort or placebo).

Possible ovulation was defined as a serum progesterone >3ng/ml within 2 weeks of Days 9-12 of the menstrual cycle.

Clearance (L/hr) of Levonorgestrel Over 24 Hours for Each Dosage Group and Each Study Session. [ Time Frame: Clearance at 24 hours from dosing ] [ Designated as safety issue: No ]

Average and standard deviation for Clearance (L/hr) of Levonorgestrel study for each dosage group and each study session.

This group had baseline pharmacokinetic studies after an oral dose of levonorgestrel (LNG) 1.5 mg, then took a placebo herb daily for 4-6 weeks, during which time pharmacokinetic studies were repeated after an oral dose of LNG 1.5 mg

Dietary Supplement: Placebo Control (Placebo Herb)

Placebo herb three times daily (ground cellulose) for 4-6 weeks

Drug: Levonorgestrel

Levonorgestrel in a single oral dose

Active Comparator: Levonorgestrel 1.5 with SJW 900 mg

This group had baseline pharmacokinetic studies after an oral dose of levonorgestrel (LNG) 1.5 mg, then took St. John's Wort (SJW) 900 mg a Day orally for 4-6 weeks, during which time pharmacokinetic studies were repeated after an oral dose of LNG 1.5 mg

Dietary Supplement: St. John's Wort

St. John's Wort (Hypericum perforatum) orally or 4-6 weeks

Drug: Levonorgestrel

Levonorgestrel in a single oral dose

Active Comparator: Levonorgestrel 2.25 with SJW 900 mg

This group had baseline pharmacokinetic studies after an oral dose of levonorgestrel (LNG) 1.5 mg, then took a St. Johns's Wort 300 mg capsules three times daily for 4-6 weeks, during which time pharmacokinetic studies were repeated after an oral dose of LNG 2.25 mg

Dietary Supplement: St. John's Wort

St. John's Wort (Hypericum perforatum) orally or 4-6 weeks

Drug: Levonorgestrel

Levonorgestrel in a single oral dose

Active Comparator: Levonorgestrel 1.5 with SJW 1500 mg

This group had baseline pharmacokinetic studies after an oral dose of levonorgestrel (LNG) 1.5 mg, then took a St. Johns's Wort 300 mg capsules five times daily for 4-6 weeks, during which time pharmacokinetic studies were repeated after an oral dose of LNG 1.5 mg

Dietary Supplement: St. John's Wort

St. John's Wort (Hypericum perforatum) orally or 4-6 weeks

Drug: Levonorgestrel

Levonorgestrel in a single oral dose

Detailed Description:

In the last decade, St. John's wort has become one of the most commonly used botanicals. Levonorgestrel is a form of progesterone, a female hormone involved in conception. It can be given as both a pill and an injection and is used for contraception and for the treatment of endometriosis. However, evidence suggests that St. John's wort may reduce the effectiveness of the contraceptive hormone levonorgestrel. This study will determine whether interactions between St. John's wort and levonorgestrel reduce the effectiveness of the hormone. This study will also determine whether a higher dose of levonorgestrel will override the effects of St. John's wort.

All participants will receive a single dose of levonorgestrel between Days 9 and 12 of their first menstrual cycle after entering this study. Blood and urine collection will occur immediately after the levonorgestrel is given and every week until participants' next menstrual cycle to determine the levels of reproductive hormones in participants' bodies.

At the beginning of participants' next menstrual cycle, they will be randomly assigned to one of four groups and receive either St. John's wort or placebo for 6 weeks. Group 1 will receive a placebo; Groups 2 and 3 will receive a standard dose of St. John's wort (900 mg per day); and Group 4 will receive an increased dose of St. John's wort (1500 mg per day). After 6 weeks, Groups 1, 2, and 4 will receive 150 mcg levonorgestrel; and Group 3 will receive 225 mcg levonorgestrel. Blood and urine collection will occur immediately after levonorgestrel is given and every week until participants' next menstrual cycle.

Eligibility

Ages Eligible for Study:

18 Years to 30 Years

Genders Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Criteria

Inclusion Criteria:

Body mass index (BMI) between 20 and 25

Regular menstrual cycles for at least 3 months prior to study entry

Exclusion Criteria:

Current use of foods, herbs, vitamins, over-the-counter supplements, or any medications that could alter pharmacokinetics of other drugs

Medical contraindications to the use of contraceptives

Contacts and Locations

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To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00131885